Kill the Virus, Stop the Cancer

Researchers have for the first time shown that as many as 1.3 million cases of cancer a year may one day be successfully treated or even prevented by targeting and destroying the viruses that cause them.

Scientists at the Albert Einstein College of Medicine of Yeshiva University in New York City say the finding could pave the way for conquering human cancers that are linked to preexisting viral infections, among them liver cancer (caused by the hepatitis B and C viruses), cervical cancer (from human papillomavirus) and lymphomas caused by the Epstein–Barr virus.

They key, they say, is to find and destroy the viruses before they turn cancerous. In an attempt to do this, the researchers used a technique known as radioimmunotherapy in which radioisotopes (unstable elements that release radiation) mounted on antibodies (protein molecules akin to infection search-and-destroy missiles) are injected into the body. Once inside, researchers found that the antibodies zeroed in on their targets—viral antigens—and the radioisotopes destroyed nearby cancer cells without damaging surrounding healthy tissue.

Viral antigens are proteins produced by virus-infected cells that can cause those cells to go berserk and start multiplying out of control, thereby becoming cancerous. Antibodies are immune proteins with binding sites that can fit like puzzle pieces into corresponding sites on foreign viral or bacterial antigens and disable them (triggering other immune responses). The problem with viruses that typically cause cancer, though, is that they tend hide out of reach—inside of rather than on the surface of cells. The Einstein researchers, however, found a way around that.

"We had a hunch that rapidly growing tumors can 'outgrow' their blood supply, resulting in dead tumor cells that might spill their viral antigens amongst the living cancer cells," said co-senior study author Arturo Casadevall, chair of Einstein's Microbiology & Immunology department. "So we hoped that by injecting antibodies hitched to isotopes into the blood that they'd be carried deep into the tumor mass and would latch onto these now-exposed antigens. Then the blast of radiation emitted by the radioisotope would destroy the tumor cells nearby."

The researchers tested their theory on mice, attaching the radioisotope rhenium 18 to antibodies that attack E6, a viral antigen produced by virtually all cervical cancer cells. They prepared a similar weapon against liver cancer by piggybacking rhenium 18 on antibodies that target HBx, a viral antigen made by cancerous liver cells. The mice, which had been injected with human cervical and liver cells, were treated with the appropriate radioimmunotherapy.

In both cases, researchers report in PLoS ONE the therapies significantly slowed tumor growth compared with results in untreated mice. In the animals with cervical cancer, the tumors not only stopped growing but some actually shrunk.

"Radioimmunotherapy not only worked against these cancers but, in addition, the radioactivity was confined entirely to the tumor masses, leaving healthy tissues undamaged," said senior study co-author Ekaterina Dadachova, an associate professor of nuclear medicine and of microbiology and immunology at Einstein.

Dadachova, a pioneer in the use of radioimmunotherapy against infectious diseases, previously successfully turned it on a streptococcal bacterium that causes pneumonia. Last year, she and her colleagues showed that the therapy could also be used to help halt HIV by targeting one of several viral proteins on the surface of HIV-infected cells.

"Our study has shown in principle that radioimmunotherapy can help in treating cancers caused by viruses—and, just as exciting, the approach also holds promise for cancer prevention,'' she said. "In people chronically infected with hepatitis B or C, human papillomaviruses or other viruses known to cause cancer, radioimmunotherapy could potentially eliminate virus-infected cells before they're able to transform into cancer cells."